A Laser Capture Microdissection (LCM) system has been developed in collaboration with NCI, NICHD, and OD. The LCM system permits one-step procurement of selected human cell populations from a much larger section of complex, heterogeneous tissue. The targeted regions are comprised of either cells from a specific pathology, or normal control cells. Due to the high purity of the dissected tissue, there is a significant increase in value of subsequent genetic analysis results. Prior to the development of LCM, dissected tissues were often contaminated by wrong cells, therefore limiting the practical value of downstream molecular analysis. The SPCSG is responsible for many aspects of the LCM system design which are critical to the success, and advancement, of the technology. Example SPCSG design and development responsibilities include: laser diode control electronics, instrumentation computer control software, image and data archiving, system automation, system networking, and telemedicine.A cDNA Microarray system has been developed in collaboration with NHGRI, NCI, NIEHS, and OD. The cDNA Microarray system is used to study thousands of genes simultaneously, an advance that will help examine the complex relationships between individual genes. The cDNA Microarray system is being used to study the development and progression of cancer, and the experimental reversal of tumorigenicity, which are both accompanied by complex changes in patterns of gene expression. The system is comprised of an Arrayer and a Scanner. The Arrayer generates high-density microarrays of expressed sequence tags (ESTs) on microscope slides. The Scanner provides a means of obtaining quantitative measures of the extent of hybridization of flourescently tagged genetic messenger molecules to the ESTs in the microarray. Previously unrecognized alterations in the expression of specific genes have been discovered with this system. The SPCSG is responsible for many aspects of the cDNA Microarray system design. Some example responsibilities are: custom electronics design for signal conditioning and data acquisition; motion control hardware development; custom software specification for system control and data processing; and system integration.An Ultra-Rapid Scanning Spectrometer (URSS) system has been developed in collaboration with NHLBI and OD. The URSS system was designed to obtain data, through the measurement of time-resolved absorption spectra, on the kinetic reaction mechanisms of biological preparations such as cytochrome oxidase and bacteriorhodopsin. Although the URSS system has proven to be a powerful tool over the years, studies have shown that a higher performance URSS system is required. Consequently, the research and design of an advanced, second-generation, URSS instrument has been initiated. With the exception of the optics subsystem, the SPCSG is responsible for the development of the entire system. Design and development areas include: photodiode analog interface circuitry, data acquisition and timing circuitry, system integration, and instrument software development. An Electron Paramagnetic Resonance (EPR) Spectrometer/Imager system has been developed in collaboration with NCI and NIDDK. The EPR system was designed to perform noninvasive in-vivo imaging and spectroscopy. The EPR system represents the first reported low frequency pulsed EPR spectrometer/imager to be constructed for the purposes of in-vivo imaging of free radicals. Over the recent years, this project has required considerable electrical engineering research and development. For example, a specialized 300 Megasamples per second digitizer-averager was designed by SPCSG staff to increase the signal-to-noise ratio while maintaining high pulse excitation repetition rates. Techniques developed on this project have stimulated developments in other laboratories. The SPCSG design responsibilities on this project include: data acquisition design, digital signal processing algorithm development, radio-frequency design, control software development, and system integration. A Chromosome Microdissection system is being developed in collaboration with NHGRI and OD. The Chromosome Microdissection system is required to cut and recover fragments out of stained chromosomes. These DNA fragments are ultimately used as reagents for detecting the gene regions that were present in the dissected portion of the original chromosome. This technology will facilitate the survey of a large number of cancer cells to identify the genes consistently amplified in various kinds of cancers. The Chromosome Microdissection system will automate a large portion of the process, resulting in higher throughput, greater accuracy, and shorter training periods for users. The SPCSG is responsible for many aspects of the Chromosome Microdissection system design. Some example responsibilities are: motion control hardware development, custom software development for process and motion control, image acquisition and processing, and system integration.A Tissue Microarray system is being developed in collaboration with NHGRI. New techniques, such as cDNA microarray analysis, have enabled measurement of the expression of thousands of genes in a single experiment. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic, and therapeutic importance of each of the emerging gene candidates. To meet this need, the high-throughput automated Tissue Microarray system is being developed to facilitate gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor microarray. In addition to the arraying system development, automation of the microarray analysis is critical to the success of the technology. Automation is especially important in the analysis of gene copy number alterations by fluorescence in situ hybridization (FISH).